Cardiovascular disease due to atherosclerosis remains the leading cause of death in the United States. Clinical symptoms and morbidity that result from atherosclerotic disease are due to plaque instability and are manifested as ulceration, thrombosis and/or intraplaque hemorrhage. Much research has been directed at understanding the atherogenesis, the progression of the disease and the final events that lead to heart attack or stroke. However, relatively little is known about how to identify high risk lesions in vivo noninvasively and to monitor the lesion progression longitudinally. This proposal presents a plan to measure the atherosclerotic plaque volume in MR images and to assess the power of MRI in detecting plaque characteristics that are associated with clinical symptoms. We focus our study on advanced lesions at the carotid bifurcation due to 1) their close association to stroke, 2) their accessibility by high resolution MRI techniques, and 3) the accessibility of carotid samples due to carotid endarterectomy that provides us with excellent opportunity to verify the MRI results by examining the samples histologically. The long term goal of this project is to use high resolution MRI in patients with hemodynamically significant (greater than 70 percent diameter reduction) carotid stenoses to differentiate those plaques that will lead to the development of thrombosis/embolization and stroke. At present there are no reliable means to either measure the plaque volume in vivo or to assess the characteristics of plaques in vivo. The specific aims are: 1) to test whether in vivo MRI can be used to measure the atherosclerotic volume, and 2) to test whether in vivo MRI can identify lesions with thin fibrous cap and a necrotic core. We propose to determine the accuracy of MRI plaque volume measurement and the sensitivity and specificity of MRI in the detection of different types of lesions. Accurate diagnosis of different plaque types has particular clinical relevance, as a weakened fibrous cap covering a necrotic core is thought to be structually weak, and may precede the events of plaque rupture and thromboembolic occlusion, which in the carotid artery may result in stroke. The ability to accurately measure plaque volumes and to distinguish the structural characteristics of advanced lesions of atherosclerosis in vivo may provide a noninvasive mechanism to follow the evolution of plaque progression and to detect lesions that may put individuals at greater risk of clinical events.